TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

The overall goal of this procedure is to explore cortical motor plasticity and how it relates to typical and atypical neural development using non-invasive transcranial magnetic stimulation. This is accomplished by first locating the subject's M1 motor hotspot for the first dorsal interros muscle and determining both resting and active motor threshold. The second step of the procedure is to obtain baseline corticospinal excitability.

The third step of the procedure is to apply theta burst stimulation. The final step of the procedure is to evaluate resultant corticospinal excitability. Ultimately, results can be obtained that show differences in the effects of theta birth stimulation on corticospinal excitability in subjects with neurodevelopmental disorders, through the variation between baseline and post stimulation excitability.

Today, we will demonstrate a type of transcranial magnetic stimulation called theta birth stimulation. This method can help answer key questions in the field of clinical cognitive neuroscience, such as how mechanisms of plasticity contribute to the pathological, neurological and behavioral phenotypes characteristic of specific developmental disorders. Before beginning this protocol, access the subject's MRI image using your frameless stereotype setup Set up.

This anatomical model will be used to mark specific cranial locations and ensure the same location is stimulated each time Before beginning the theta burst stimulation, it is first necessary to determine the location of the subject's primary motor cortex. To begin seat the subject in a comfortable chair adjacent to the TMS equipment. Be sure to screen the subject to assure that there are no counter indications to TMS and explain the details of the protocol.

Also, register the subject's location using the stereotactic equipment and introduce him or her to the TMS setup. Discharge a few pulses so that he or she is familiar with the clicking noise and tapping sensation. Next, set the subject up for the experiment by first asking them to present his or her right hand so that surface electrodes can be applied to the dorsal interros muscle.

Before applying the electrodes, be sure to clean the skin to ensure proper registration. If the dorsal interros muscle is difficult to locate, ask the subject to make a pinching motion or to move his or her index finger back and forth. As this should make the muscle easier to find.

Apply EMG surface electrodes over the first dorsal inters muscle of the right hand so that the muscle twitches caused by TMS can be recorded. Also, place a ground electrode on the meaty portion of the subject's forearm. Check your recording equipment to assure that all the surface electrodes are providing a good signal without too much noise.

Both the subject and the technician should insert earplugs at this point for hearing protection. Now we are ready to determine the location of the subject's left motor cortex hand area. Although this area differs slightly for everyone, it'll generally be around 3.5 centimeters.

Rost lateral of the cranial vertex with stimulation intensity set to 50%Explore a small grid around this region until a motor hotspot is located by moving the coil in small increments while watching. For the maximal MEP. Also adjust the stimulation, intensity, and angle of stimulation as needed.

Once M1 has been identified, be sure to mark its location using the stereotactic equipment if available. If not, a non-toxic grease pen can be used to temporarily mark the subject's scalp. The next step in this protocol is to determine the subject's resting motor threshold.

Readjust the system back to 50%power if needed, and begin single pulse stimulation to the same location while measuring the resultant motor evoked potentials. Adjust the power up or down until an MEP of greater than 50 microvolts is produced in exactly five out of 10 consecutive pulses. Record this power level as the subject's resting motor threshold.

Next, ask the subject to gently pinch his or her right fore finger and thumb together using about 20%pressure while the subject holds. This pinching position begins single pulse stimulation at 50%power over the same M1 location. Measure and record the resultant meps.

Now adjust the power up or down until an MEP of greater than 200. Microvolts is produced on exactly five out of 10 consecutive pulses. This power level is the subject's active motor threshold.

Finally, determine a subject's baseline, MEP by stimulating the motor hotspot at 120%resting motor threshold with 10 single pulses measuring the MEP. After each pulse average the MEP values from three batches of 10 pulses. Now that the subject's threshold levels have been determined, the system can be set up for stimulation.

We will be utilizing standard theta burst parameters being three pulses at 50 hertz at an intensity of 80%active motor threshold for 200 millisecond intervals to administer intermittent TBS, which has been shown to facilitate cortical activity. Generate a two second stimulation, train at the aforementioned parameters, followed by eight seconds of no stimulation. Repeat for 190 seconds, which is a total of 600 pulses to administer continuous theta burst, which has been shown to inhibit cortical activity.

Generate an uninterrupted stimulation train at the aforementioned parameters for 47 seconds, which also amounts to a total of 600 pulses. Assure that the subject is comfortable and ready to begin as the rest of the protocol should be completed without interruption. Ask him or her to remain still and relaxed.

Place the coil over the earlier established M1 motor hotspot and administer either ITBS or CTBS. Here we are administering CTBS. Be sure the coil remains in the correct position throughout stimulation.

Following theta. Birth stimulation, immediately begin to determine post stimulus motor revoked potentials so that the transient effects of TMS can be assessed. To do this.

First, set the TMS machine to deliver single pulses at 120%resting motor threshold. Now again, place the coil over the subject, same motor hotspot, assure that the coil is in the exact same location that was stimulated with TBS. Stimulate with 10 single pulses using the same electrode setup used during the previous step to measure and record the resulting batch of 10 MEP levels.

These ME Ps should then be averaged and recorded as the result at this time point. Next, use the parameters to stimulate at 11 time points post TBS five minutes, 10 minutes, 20, 30, 40, 50, 60, 75, 91 0 5, and finally 120 minutes post stimulation, measure and collect new 10 pulse batch recordings and averages at each time point. Once completed, remove the surface electrodes and allow the subject to remove the earplugs and stand up.

Be sure to thank him or her for participating in the experiments. Also, ask the subject to return for a future TMS session so that other TBS parameters can be investigated. The results of the TMS session will depend on the TBS pattern used.

Here we see some representative results from a group when utilizing an intermittent theta birth stimulation pattern. One should notice an increase in MEP values for duration reflecting the subject's natural state of plasticity as seen here. Likewise, when utilizing a continuous the of birth stimulation pattern, one should notice a decrease in MEP values for duration, reflecting the subject's natural state of plasticity Following this procedure.

Other procedures such as behavioral tasks, pharmaceutical interventions, and or additional stimulation paradigms can be performed in order to answer additional questions such as how does abnormal plasticity manifest and how can it be treated?